Monoclonal Antibodies

CD20 is only dimly expressed on CLL cells. In advanced CLL, treatment with rituximab at standard doses results in only a 15% response rate.13 Higher doses can achieve higher response rates, but PFS is generally short.14,15 Furthermore, the use of rituximab earlier in treatment is likely to result in rituximab resistance. Thus, as a single agent, rituximab has a limited role in the treatment of advanced CLL.

Alemtuzumab has been explored as a treatment for relapsed or refractory CLL in several clinical trials. A consistent response rate of 30-40%, and PFS of approximately 1 year in responders, is reported by these studies when the drug is administered at 30 mg as an IV infusion three times a week for 3-4 months.16-20 Alemtuzumab is particularly useful in the treatment of CLL characterized by 17p deletions that are known to be chemotherapy resistant.21 The drug is associated with significant and sometimes severe infusion reactions, however. These reactions are muted, with no apparent loss of efficacy, when alemtuzumab is administered sub-cutaneously, though this administration route in no way abrogates its immunosuppressive side effects.2223 Patients treated with alemtuzumab require antimicrobial prophylaxis against bacteria, Pneumocystis jeroveci, and Herpes viruses.24 In addition, there is a substantial risk of cytomegalovirus reactivation and infection that requires a high level of suspicion for fevers of undetermined origin at a minimum, and possibly oral prophy-laxis.25-27

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